Triggers of self-focused attention: an ecological momentary assessment study.

BACKGROUND: Self-focused attention (SFA) is a major maintenance factor of social anxiety disorder. The two types of SFA, the observer perspective and self-focus on body sensation, increase anxiety in individuals with high levels of social anxiety. However, the triggers of each SFA remain unclear. This study used ecological momentary assessment to identify the factors that elicit SFA in real-life social scenarios. METHODS: The study obtained 316 samples from 22 Japanese university students (4 male:18 female) with high social anxiety who completed momentary measures of stimulus perception and two types of SFA for 10 days. Links to online questionnaires were sent to the participants via e-mails 3 times a day. First, multilevel single regression analyses were used to identify the stimuli that induced the two types of SFA. Between-level interaction with gender was done to determine the effect of gender biasing on the female participants. Next, for the variables that were significantly predictive in these analyses, multilevel multiple regression analyses were conducted with fear of each stimulus as a control variable. RESULTS: Perception of gaze, evaluation, and authority predicted SFA from the observer perspective. Perception of gaze also predicted self-focus on body sensation. In addition, the perception of positive response and that of stranger predicted self-focus on body sensation depended on gender, implying that the positive response perception of female participants predicted self-focus on body sensation. After controlling for corresponding fear, gaze perception predicted both SFAs, and the perception of authority predicted SFA from the observer perspective. In addition, after controlling for relevant fear, the perception of positive response of female participants predicted self-focus on body sensation. In contrast, the fear of evaluation but not the perception of evaluation predicted SFA from the observer perspective. CONCLUSIONS: The perception of gaze is the most powerful trigger of the two types of SFA, even after controlling for fear of gaze in real-life social scenarios for individuals with social anxiety. SFA from the observer perspective is also triggered by the perception of authority and fear of evaluation. The role of perception of positive responses or strangers should be re-evaluated after correcting for gender imbalance. (350 words / 350 words).

Effect of therapeutic exercise on the balance of patients with progressive supranuclear palsy: A pilot study.

Background: Progressive supranuclear palsy (PSP) is a parkinsonian-like progressive neurodegenerative syndrome. Key clinical features include ocular motor dysfunction, postural instability, and cognitive dysfunction. Maintaining and improving balance function and gait function are very important for patients with PSP with severe postural dysfunction and repeated falls. In addition, patients with PSP have a poor response to pharmacological treatment; hence, rehabilitation is a key approach in dealing with this syndrome. However, no conclusion on the beneficial effects of rehabilitation for patients with PSP have been established in the literature. Objectives: The effectiveness of multiple therapeutic exercise program with probable or possible PSP according to the Movement Disorder Society criteria for the clinical diagnosis of PSP was validated. Methods: Participants underwent multiple therapeutic exercise program customized for each participant, including resistance training, balance training, and walking exercises that were performed for 60-80 minutes a day, 5 days a week for 4 weeks. The outcomes measured were as follows: pull test, Berg Balance Scale (BBS), timed up and go test (TUG), and gait speed test. Results: A total of 117 patients with PSP were enrolled and the analysis was performed on 20 patients with probable PSP. Four-week rehabilitation significantly improved pull test (p = 0.034) and BBS scores (p = 0.001). There were no significant differences both TUG (p = 0.502) and gait speed (p = 0.813). Conclusion: The multiple therapeutic exercise program had beneficial effects on balance performance in patients with PSP in 4 weeks and could be an essential element in their rehabilitation. Although this pilot study was conducted without a control group, it provided valuable information for future prospective randomized controlled trials.

The combination of short-step and wide-based gait is a gait characteristic in progressive supranuclear palsy: a retrospective, cross-sectional study.

PURPOSE: Like Parkinson's disease (PD), gait disturbance is a major problem in progressive supranuclear palsy (PSP). Despite limited studies investigating the gait characteristics, we hypothesize that they differ from PD owing to the involvement of different brain lesions. Hence, this study aims to investigate the gait characteristics in patients with PSP by comparing with healthy older adults and patients with PD. METHODS: We identified 27 PSP patients, 25 PD patients, and 25 neurologically healthy older persons. Using a device that detected the distribution of foot pressure during walking, we analyzed gait variables and measured the walking speed (cm/s), cadence (steps/min), step length (cm), step width (cm), foot angle (°), and gait cycle time (s). Additionally, we calculated the coefficient of variation (CV, %) on walking speed and cadence and analyzed the gait characteristics by the PSP subtypes. RESULTS: In PSP and PD, the walking speed was slower and the step length was shorter than healthy controls. The CV of cadence in PSP was higher than healthy controls and PD. In PSP, the step width and foot angle were higher than healthy controls and PD. The gait cycle time was longer in PSP and PD than healthy controls. PSP with progressive freezing gait tended to display a faster walking speed. Furthermore, PSP with parkinsonism-resembling idiopathic PD tended to exhibit the larger step width and foot angle compared with PSP-Richardson's syndrome. CONCLUSION: This study suggests that the gait of PSP was unstable with parkinsonism and wide-based, which might be similar to combining features of PD and cerebellar disorders.

Management of afatinib-induced stomatitis.

Severe stomatitis may lead to the need to interrupt or discontinue cancer therapy and, thus, may affect control of the primary disease. Stomatitis may also increase the risk of local and systemic infection and significantly affects the quality of life and the cost of care. The present study was conducted to evaluate the efficacy of two traditional herbal medicines in controlling treatment-induced stomatitis in a small cohort of lung cancer patients treated with afatinib. All patients who were treated with afatinib for epidermal growth factor receptor (EGFR) mutated nonsmallcell lung cancer (NSCLC) between January, 2015 and March, 2016, were included in this study. During the study period, a total of 14 NSCLC patients were treated with afatinib, an EGFR-tyrosine kinase inhibitor (TKI). Two patients already had stomatitis at the time of initiation of afatinib therapy; among the remaining 12 NSCLC patients, 2 (16.7%) developed stomatitis. All the lesions in the 4 patients who developed stomatitis were completely alleviated after 2 weeks of therapy with Aznol mouthwash, a chamomile extract with anti-inflammatory effects, and Hangeshashinto, a traditional herbal (Kampo) medicine. Afatinib therapy was re-initiated, but none of the patients developed stomatitis thereafter. To the best of our knowledge, this is the first report evaluating oral care and management of stomatitis. This type of care and treatment may reduce the incidence of complications associated with EGFR-TKI therapy.

Roles of thioredoxins in the obligate anaerobic green sulfur photosynthetic bacterium Chlorobaculum tepidum.

Thioredoxin is a small ubiquitous protein that is involved in the dithiol-disulfide exchange reaction, by way of two cysteine residues located on the molecule surface. In order to elucidate the role of thioredoxin in Chlorobaculum tepidum, an anaerobic green sulfur bacterium that uses various inorganic sulfur compounds and H(2)S as electron donors under strict anaerobic conditions for growth, we applied the thioredoxin affinity chromatography method (Motohashi et al., 2001). In this study, 37 cytoplasmic proteins were captured as thioredoxin target candidates, including proteins involved in sulfur assimilation. Furthermore, six of the candidate proteins were members of the reductive tricarboxylic acid cycle (pyruvate orthophosphate dikinase, pyruvate flavodoxin/ferredoxin oxidoreductase, alpha-oxoglutarate synthase, citrate lyase, citrate synthase, malate dehydrogenase). The redox sensitivity of three enzymes was then examined: citrate lyase, citrate synthase, and malate dehydrogenase, using their recombinant proteins. Based on the information relating to the target proteins, the significance of thioredoxin as a reductant for the metabolic pathway in the anaerobic photosynthetic bacteria is discussed.

SoxAX binding protein, a novel component of the thiosulfate-oxidizing multienzyme system in the green sulfur bacterium Chlorobium tepidum.

From the photosynthetic green sulfur bacterium Chlorobium tepidum (pro synon. Chlorobaculum tepidum), we have purified three factors indispensable for the thiosulfate-dependent reduction of the small, monoheme cytochrome c(554). These are homologues of sulfur-oxidizing (Sox) system factors found in various thiosulfate-oxidizing bacteria. The first factor is SoxYZ that serves as the acceptor for the reaction intermediates. The second factor is monomeric SoxB that is proposed to catalyze the hydrolytic cleavage of sulfate from the SoxYZ-bound oxidized product of thiosulfate. The third factor is the trimeric cytochrome c(551), composed of the monoheme cytochrome SoxA, the monoheme cytochrome SoxX, and the product of the hypothetical open reading frame CT1020. The last three components were expressed separately in Escherichia coli cells and purified to homogeneity. In the presence of the other two Sox factors, the recombinant SoxA and SoxX showed a low but discernible thiosulfate-dependent cytochrome c(554) reduction activity. The further addition of the recombinant CT1020 protein greatly increased the activity, and the total activity was as high as that of the native SoxAX-CT1020 protein complex. The recombinant CT1020 protein participated in the formation of a tight complex with SoxA and SoxX and will be referred to as SAXB (SoxAX binding protein). Homologues of the SAXB gene are found in many strains, comprising roughly about one-third of the thiosulfate-oxidizing bacteria whose sox gene cluster sequences have been deposited so far and ranging over the Chlorobiaciae, Chromatiaceae, Hydrogenophilaceae, Oceanospirillaceae, etc. Each of the deduced SoxA and SoxX proteins of these bacteria constitute groups that are distinct from those found in bacteria that apparently lack SAXB gene homologues.

Binary reducing equivalent pathways using NADPH-thioredoxin reductase and ferredoxin-thioredoxin reductase in the cyanobacterium Synechocystis sp. strain PCC 6803.

Thioredoxin (Trx) is a small ubiquitous protein involved in the disulfide-dithiol exchange reaction occurring in cells and organelles. In vivo, Trx is reduced by Trx reductase using NADPH or photosynthetically produced reducing equivalents, and the reduced form Trx takes on the physiological functions. In the cyanobacterium Synechocystis sp. PCC6803, two Trx reductases, ferredoxin-Trx reductase (FTR) and NADPH-Trx reductase (NTR), and four typical Trx isoforms have been identified by genomic analysis. Based on analysis of the physiological features of the Trx reductase disruptants, we found that the NTR-Trx pathway is important for the antioxidant system, whereas the FTR-Trx pathway may play a more important role in the control of cell growth rate. In addition, by quantification of Trx abundance in the wild-type and the disruptant Synechocystis cells, we found that the gene product of slr0623, the homolog of m-type Trx in higher plants, is the most abundant Trx, and that accumulation of Trx isoforms occurs dependent on the expression of the other redox-related proteins. A study of the binary reducing equivalent pathways in cyanobacterial cells is reported here.

Towards a functional dissection of thioredoxin networks in plant cells.

Thioredoxins are a ubiquitous family of redox equivalent mediators, long considered to possess a limited number of target enzymes. Recent progress in proteomic research has allowed the identification of a wide variety of candidate proteins with which this small protein may interact in vivo. Moreover, the activity of thioredoxin itself has been recently found to be subject to regulation by posttranslational modifications, adding an additional level of complexity to the function of this intriguing enzyme family. The current review charts the technical progress made in the continuing discovery of the numerous and diverse roles played by these proteins in the regulation of redox networks in plant cells.

Thioredoxin-h1 reduces and reactivates the oxidized cytosolic malate dehydrogenase dimer in higher plants.

Cytosolic malate dehydrogenase (cytMDH) was captured by thioredoxin affinity chromatography as a possible target protein of cytosolic thioredoxin (Yamazaki, D., Motohashi, K., Kasama, T., Hara, Y., and Hisabori, T. (2004) Plant Cell Physiol. 45, 18-27). To further dissect this interaction, we aimed to determine whether cytMDH can interact with the cytosolic thioredoxin and whether its activity is redox-regulated. We obtained the active recombinant cytMDH that could be oxidized and rendered inactive. Inactivation was reversed by incubation with low concentrations of dithiothreitol in the presence of recombinant Arabidopsis thaliana thioredoxin-h1. Inactivation of cytMDH was found to result from formation of a homodimer. By cysteine mutant analysis and peptide mapping analysis, we were able to determine that the cytMDH homodimer occurs by formation of a disulfide bond via the Cys(330) residue. Moreover, we found this bond to be efficiently reduced by the reduced form of thioredoxin-h1. These results demonstrate that the oxidized form cytMDH dimer is a preferable target protein of the reduced form thioredoxin-h1 as suggested by thioredoxin affinity chromatography.

Thioredoxin affinity chromatography: a useful method for further understanding the thioredoxin network.

Thioredoxin affinity chromatography can be used to recognize the target proteins of thioredoxin or thioredoxin-related proteins in whole cells or certain cellular compartments. In the last couple of years, many potential target proteins have been identified from various organelles and organisms by this method. Based on the information on the target proteins provided by these studies, the complete thioredoxin-related redox networks can now be efficiently described.

Anti-oxidative stress system in cyanobacteria. Significance of type II peroxiredoxin and the role of 1-Cys peroxiredoxin in Synechocystis sp. strain PCC 6803.

Two antioxidant proteins, SLL1621 and SLR1198, were captured in the cyanobacteria Synechocystis sp. PCC 6803 using thioredoxin affinity chromatography, which was first applied to the survey of thioredoxin target proteins in chloroplasts (Motohashi, K., Kondoh, A., Stumpp, M. T., and Hisabori, T. (2001) Proc. Natl. Acad. Sci. U. S. A. 98, 11224-11229). They are annotated as AhpC/TSA family protein (SLL1621) and antioxidant protein (SLR1198) in CyanoBase (Nakamura, Y., Kaneko, T., Hirosawa, M., Miyajima, N., and Tabata, S. (1998) Nucleic Acids Res. 26, 63-67). Based on sequence homology analysis SLL1621 and SLR1198 are categorized into type II peroxiredoxin and 1-Cys type peroxiredoxin, respectively. In vitro interaction between SLL1621 and thioredoxin was confirmed using the recombinant proteins expressed in Escherichia coli. Furthermore, we found that SLL1621 shows remarkable glutathione-dependent peroxidase activity. Disruption of the sll1621 gene had a dramatic effect on the viability of the cyanobacterial cells even under weak light conditions (50 micromol.m(-2).s(-1)), suggesting this peroxiredoxin is essential for this cyanobacterium. In contrast, although the peroxidase activity of SLR1198 was scarcely detected, disruption of the gene, slr1198, certainly affected the growth rate of the cells. The results indicate the physiological significance of two different peroxiredoxins as an anti-oxidative stress system in cyanobacteria.